Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 815621, 22 pages http://dx.doi.org/10.1155/2013/815621 Review Article An Update on Antitumor Activity of Naturally Occurring Chalcones En-Hui Zhang,1 Ru-Feng Wang,1 Shu-Zhen Guo,2 and Bin Liu1 1 School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100102, China 2 School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China Correspondence should be addressed to Bin Liu; [email protected] Received 15 January 2013; Accepted 19 March 2013 Academic Editor: Yoshiyuki Kimura Copyright © 2013 En-Hui Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica,Sophora,Glycyrrhiza,Humulus,Scutellaria,Parartocarpus,Ficus,Dorstenia,Morus,Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. 1. Introduction biosynthesis of flavonoids. Structurally, they are a group of compounds bearing 1,3-diaryl-2-propen-1-one framework, Chalcones are one of the subclasses of flavonoid family. which consists of open-chain flavonoids in which the two Theyarecommonlyknownasyellowpigmentsinflowers, aromatic rings are joined together by three carbons in an ,- and are also widely distributed in various parts (roots, unsaturated system. Chemically, they can be easily cyclized rhizomes, heartwood, buds, leaves, flowers, and seeds) of by a Michael addition at the position of the carbonyl species of genera Angelica, Sophora, Glycyrrhiza, Humulus, to form a flavanone. The existence of double bond results Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocar- in cis and trans isomeric forms of chalcone in nature, of pus, and so forth. A wide range of biological activities which the trans form is thermodynamically stable. Chalcone have been attributed to chalcones, including antitumor, is one of the most structurally diverse groups of flavonoids antimutagenic, anti-inflammatory, antioxidant, antifungal, existing as dimmers, oligomers, Diels-Alder adducts, and antibacterial, antiprotozoal, analgesic, and gastric protective conjugates of various kinds. Additionally, the attachment of properties [1]. As for antitumor activity, chalcones exhibit varieties of hydroxyl, methoxy, and alkenyl functionalities various effects including anti-initiation, apoptosis induction, to the framework of chalcone contributes to its structural antiproliferation, antimetastasis, antiangiogenesis, and so diversity as well [3]. forth.Thisreviewsummarizesthestudiesontheantitumor During the last decade, about 90 compounds of chalcones activity of naturally occurring chalcones and their underlying with various antitumor activities were reported. They can mechanisms in detail during the past decade and also briefly be roughly categorized into 4 large groups, namely, chal- categorized these compounds on the basis of their structures. cones with O-substitution, prenylated chalcones, Diels-Alder adducts, and others. All these 90 compounds are shown in Figure 1. 2. Structures Chalcones, a term introduced by Kostanecki and Tabor 2.1. Chalcones with O-Substitution. This group of compounds [2], are considered as the precursors of flavones in the (1–26) carries a varying number of O-substituents on A-ring 2 Evidence-Based Complementary and Alternative Medicine 3 2 4 3 4 2 5 6 5 6 O 2 3 4 5 6 2 3 4 5 6 1 H H OH H OH H OH OH H H 2 OCH3 H OCH3 HOHH H H HH 3 OH H OCH3 HOHH H H HH 4 OH H OH HH HOCH3 OCH3 HH 5 OH H OH HHOCH3 OCH3 H HH 6 OH H OH HH H HOCH3 HH 7 OH CH3 OHCH3 OCH3 H H H H H 8 OCH3 HOHCH3 OHH H H HH 9 OCH3 HOHHOHH H H HH 10 OH HOHH H H H H HH 11 OCH3 HOHH H H H OHHH 12 OH HOHH H H H OHHH 13 OH HHHHOHHHOCH3 OCH3 14 OH H OCH3 HOHH H H HH 15 HOHOHH HOCH3 H OHHOCH3 16 OCH3 H OCH3 HOHH HOCH3 HH 17 OCH3 H OCH3 HOHH H OHHH 18 O--D-Glc H OH H OH H H OH HH 19 OH H OH H OH H HOH H H 20 OCH3 H OH CHO OH H H H H H 21 OH H OCH3 HHOCH3 OCH3 OCH3 HH OH O OH HO OH H O R O OH O 1 O O OH OR2 H O HO OH O OH HO R1 R2 OH O 23 CH3 CH3 22 24 HH 25 CH3 H (a) Figure 1: Continued. Evidence-Based Complementary and Alternative Medicine 3 OH O H3CO OH O OH OH O 26 3 2 4 3 5 4 2 6 5 6 O 2 3 4 5 6 2 3 4 5 6 27 HHOHHOH HPreOHOCH3 H 28 OCH3 H OH Ger OH H H H H H 29 OH Ger OH H OH H H OH H H 30 OH Pre OH PreOCH3 H H OH H H 31 OH OH HOCH H H OH H H OH 3 32 OH Pre OH H OH H H OH H H 33 OH Pre OCH3 H OH H H OH H H 34 OH Pre OCH3 H OCH3 H H OH H H 35 HH OHHHH OH H OCH3 36 HH OHHHHHOH OCH3 37 HH OHHHH OH H OCH3 38 OH Pre OH H OCH3 OH H OH H H 39 H Ger OH H OH H H OH H H 40 H H OH Pre OH HHHH H 41 HHOCH3 Pre OH HHHH H 42 OH Pre OH H H H H OH H H OH 43 OH OCH3 HHH HOH HH 44 H H OH Ger OH H H OH H H 45 OH Pre OH H H H Pre OH H H 46 OH H OH Pre H H Pre OH H H 47 H H Pre OCH3 OH H H OH H H 48 H H OCH3 Ger OH H H OH H H 49 OCH3 H OH Pre OH H H OH H H (b) Figure 1: Continued. 4 Evidence-Based Complementary and Alternative Medicine R Δ 6 R5 R1 R2 R3 R4 R5 R6 O 50 HHOH OH HH R2 HO R 1 R4 51 H H OH OH H OH Δ satd. 52 H H OH OH OH OH Δ satd. 53 OH Pre H H H H R3 O R1 R2 R3 R4 R5 R6 54 OHOCH3 H H OH H R6 R4 Δ 55 OHOCH3 H H OH H Δ satd. R3 R5 56 OH H H H OH H O R 1 57 OH H H H OH H Δ satd. 58 OCH3 OH OH H OH Pre Δ satd. 59 OH H H H H H R2 O 60 OH H H OHOCH3 H 61 OH H H H OCH3 H 62 OH H H H OH H R 2 R3 R R1 OH 2 O O H3CO R3O O R1 O R1 R2 R3 R1 R2 R3 63 OH H CH3 65 OH H Pre 64 HHPre 66 H OCH3 CH3 HO OCH3 OH OH O O O HO OH O 67 68 OH O HO O OH OH O OH O 69 70 (c) Figure 1: Continued. Evidence-Based Complementary and Alternative Medicine 5 R4 R2 OH R2 R3 R1 O R1 O R R R R R1 R2 1 2 3 4 74 OH OCH OH H 71 OH OCH3 3 75 OCH3 OH OH H 72 OCH3 OH 73 OH OH 76 OH OH OH H 77 OH OHOCH3 OH 78 OH OCH3 OCH3 H HO OH HO HO OH O O OH OH HO O O OH OH O OH OH 79 80 OH R1 HO OH HO HO O O OH O O O OH H HO H R2 OH OH R1 R2 O 81 Pre H OH 83 82 H H OH HO OH OH HO O OH O OO OH H HO O OH OH HO OH OH O 84 85 (d) Figure 1: Continued. 6 Evidence-Based Complementary and Alternative Medicine OH OH HO O OH HO O O O O OH O HO OH HO OH OH 86 87 OH OH HO O HO O O O OH OH OH O OH O HO O HO O OH OH HO HO OH OH 88 89 OH OH HO HO OCH3 OH OH R2 R OH O O OCH3 R1 OH O R HO OH 94 OH 95 OCH3 R1 R2 90 OH OH OH O 91 H OH 92 OH H HO 93 H H OH HO OH OCH HO 3 Δ O OH 97 Δ satd. OH OH O 98 96 (e) Figure 1: Continued. Evidence-Based Complementary and Alternative Medicine 7 OH HO OH O OH HO O O O HO HO OH 99 (f) Figure 1: Structures of chalcones. and B-ring, including hydroxyl and methoxy groups. These 3.1. Cytotoxicity. In most cases, cell cytotoxicity was moni- groups are usually located at C-2 ,C-4, C-6 , and C-4 and toredusingtheMTTorMTSassay.Treatmentofcellswith seldom appear at C-3 , C-5 , C-2, C-3, and C-6. In addition, chalcones can cause a decrease in cell viability, and then 2 O-glycosylated chalcones (18, 22)aswellas4O-chalcone thecellsundergorapidnecrosisoractivateaprogrammed dimmers (23–26) are also included in this group.